rs2287371
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_018718.3(CEP41):c.-5A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,611,662 control chromosomes in the GnomAD database, including 148,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.40 ( 12784 hom., cov: 33)
Exomes 𝑓: 0.43 ( 135254 hom. )
Consequence
CEP41
NM_018718.3 5_prime_UTR
NM_018718.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.891
Genes affected
CEP41 (HGNC:12370): (centrosomal protein 41) This gene encodes a centrosomal and microtubule-binding protein which is predicted to have two coiled-coil domains and a rhodanese domain. In human retinal pigment epithelial cells the protein localized to centrioles and cilia. Mutations in this gene have been associated with Joubert Syndrome 15; an autosomal recessive ciliopathy and neurological disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
Variant 7-130440971-T-G is Benign according to our data. Variant chr7-130440971-T-G is described in ClinVar as [Benign]. Clinvar id is 261053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-130440971-T-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP41 | NM_018718.3 | c.-5A>C | 5_prime_UTR_variant | 1/11 | ENST00000223208.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP41 | ENST00000223208.10 | c.-5A>C | 5_prime_UTR_variant | 1/11 | 1 | NM_018718.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.401 AC: 60889AN: 151990Hom.: 12758 Cov.: 33
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GnomAD3 exomes AF: 0.458 AC: 114309AN: 249758Hom.: 27525 AF XY: 0.458 AC XY: 61926AN XY: 135146
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GnomAD4 exome AF: 0.425 AC: 620347AN: 1459554Hom.: 135254 Cov.: 43 AF XY: 0.428 AC XY: 310923AN XY: 726204
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GnomAD4 genome ? AF: 0.401 AC: 60964AN: 152108Hom.: 12784 Cov.: 33 AF XY: 0.405 AC XY: 30127AN XY: 74352
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Joubert syndrome 15 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
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CADD
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DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at